A de novo ARIH2 gene mutation was detected in a patient with autism spectrum disorders and intellectual disability

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 9, 2024

Abstract E3 ubiquitin protein ligase encoded by ARIH2 gene catalyses the ubiquitination of target proteins and plays a crucial role in posttranslational modifications across various cellular processes. As prior documented, mutations genes involved process are often associated with autism spectrum disorder (ASD) and/or intellectual disability (ID). In current study, de novo heterozygous mutation was identified splicing intronic region adjacent to last exon using whole exome sequencing (WES). We hypothesize that this mutation, found an ASD/ID patient, disrupts Ariadne domain which is autoinhibition enzyme. Predictive analyses elucidated implications novel confirmed its autosomal dominant inheritance model. Nevertheless, we cannot exclude possibility other genetic factors, undetectable WES, such as non-coding regions polygenic risk inter-allelic complementation, may contribute patient's phenotype. This work aims suggest potential relationship between detected both ASD ID, even though functional studies combined new approaches will be necessary validate hypothesis.

Language: Английский

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Genome-Wide Analysis of Genetic Predispositions Linked to Damaged Membranes and Impaired Fertility as Indicators of Compromised Sperm–Egg Interaction Mechanisms in Frozen–Thawed Rooster Semen

Frontiers in Bioscience-Scholar, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 22, 2025

Background: Cryopreservation cannot be widely used for rooster sperm due to high incidences of cryoinjury, including damage membranes. Thus, cryopreserved has limited use low motility and reduced fertilizing ability, which disrupts the mechanisms involved in sperm–egg interactions. Previously, we an Illumina 60K single-nucleotide polymorphism (SNP) array search genes associated with quality, before after freeze–thawing. As a continuation these genome-wide association studies (GWAS), present investigation denser 600K SNP chip. Consequently, screen depth was expanded by many markers cryo-resistance while more candidate were identified. our study aimed identify associations ejaculate quality indicators, those concerning membrane damage. Methods: We selected indicators freezing–thawing using samples from proprietary cryobank collection created preserve generative germ cells rare endangered breeds chickens other animal species. A total 258 ejaculates 96 roosters 16 different analyzed. Moreover, respective DNA isolated genotyping Affymetrix® Axiom® high-density array. Results: In total, 31 SNPs 26 characteristics damage, progressive motility, cell respiration induction 2,4-dinitrophenol. particular, identified ENSGALG00000029931 gene as PHF14 ARID1B damaged membranes, KDELR3, DDX17, DMD, CDKL5, DGAT2, ST18, FAM150A, DIAPH2, MTMR7, NAV2, RAG2, PDE11A, IFT70A, AGPS, WDFY1, DEPDC5, TSC1, CASZ1, PLEKHM2 induction. Conclusions: Our findings provide important information understanding genetic basis integrity traits that can potentially compromise These are relevant persistence fertility thawing previously frozen semen.

Language: Английский

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Reclassification of candidate splicing variants refines clinically conflicting interpretations inSLC26A4-associated hearing loss

Journal of Medical Genetics, Journal Year: 2025, Volume and Issue: unknown, P. jmg - 110425

Published: May 11, 2025

Purpose Variants in the human SLC26A4 gene are a major cause of hereditary hearing loss. Many splice site variants have been identified, but their pathogenicity is not well understood. Methods In accordance with guidelines from American College Medical Genetics and Genomics Association for Molecular Pathology, we analysed spectrum variants. We performed silico analysis vitro splicing assays to evaluate novel or known uncertain significance that may contribute aberrant alternative splicing. Results cohort 178 patients carrying variants, selected 202 loss without inner ear malformations who underwent testing, identified total 50 Among these, 10 intronic potentially affecting collectively accounted 54.8% allele frequency all variant types were prioritised messenger RNA (mRNA) analysis. Further investigation demonstrated four led distinct outcomes. Overall, clinical seven was reclassified, representing at least 4.34% (14/323) within our cohort. Conclusion By using standard classification results able interpret pathogenic benign direction. This approach facilitates more refined genetic counselling

Language: Английский

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Identification and characterization of a novel intronic splicing mutation in CSF1R‐related leukoencephalopathy

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: June 1, 2024

Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressing neurodegenerative disease caused by CSF1R gene mutations. This study aimed to identify and investigate the effect of novel intronic mutation (c.1754-3C>G) on splicing.

Language: Английский

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[Sperm Mosaic Variants and Their Influence on the Offspring].

PubMed, Journal Year: 2024, Volume and Issue: 55(3), P. 535 - 541

Published: May 20, 2024

Genomic mosaicism arising from mosaic variants is a phenomenon that describes the presence of cell or populations with different genome compositions germline cells an individual. It comprises all types genetic variants. A large proportion childhood disorders are defined as being

Language: Английский

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